tbuckley/cabot-search huggingface dataset:
Impact of early testing and analysis of germline genetic mutation patterns in patients with breast cancer: A single institution experience.
Authors: Aswanth Reddy, Nkolika Nwankwo, Kathleen Milam
Journal: Journal of Clinical Oncology (2023)

10613 Background: Approximately 3% of patients with breast cancer have a pathogenic or likely pathogenic variant (mutation) in a high-risk breast cancer gene, such as BRCA1, BRCA2and PALB2, which increases breast cancer risk more than fourfold. Approximately 3% have a germline mutation in a moderate-penetrance breast cancer gene, such as ATM or CHEK2, which confers a two- to threefold increased risk of breast cancer. Methods: In 2020 we started offering germline genetic testing to all newly diagnosed breast cancer patients at the time of diagnosis irrespective of their family history. Our objectives included the following: Prevalence of mutations in breast cancer patients treated at our institution. Germline mutations in patients with Ductal carcinoma in situ (DCIS). To identify if early universal germline testing affected the surgical modality. Results: A total of 525 patients were seen in the oncology clinic from January 2020 to December 2022 with a breast cancer diagnosis. The median age of diagnosis is 66 (32-91) years. Invasive ductal cancer (IDC 66 %) was the most common subtype, followed by DCIS (18%) (Table 1). Most patients had estrogen-positive cancer (82% vs. 18%), and approximately 13% had HER2-positive disease (61% HER2 low). Mutation in CHEK2 (9 patients) was our cohort's most common pathogenic mutation, followed by BRCA1 (6 patients) and MUYTH (6 patients) genes. Predominant germline mutations were identified in patients with IDC, followed by DCIS. One patient with a pure mucinous subtype had a germline pathogenic mutation (RECQL4 gene). We identified a higher percentage of pathogenic breast cancer-related mutations in patients above 60 years (63% vs. 37%) and all CHEK2 mutations were in patients above 60. Out of 41 patients with pathogenic mutations, 17 underwent a partial mastectomy, 12 had a bilateral mastectomy, and two had a unilateral mastectomy. All patients with BRCA1/2 mutation chose bilateral mastectomy, and all patients with a CHEK2 mutation underwent a partial mastectomy. Several variants of unknown significance (VUS) mutations were identified, and they followed a similar pattern, being more common in patients with IDC. VUS mutations in the ATM gene were the most reported abnormality. Conclusions: Pathogenic mutation in the CHEK2 gene is more prevalent, and we hypothesize that this finding could be related to the demographic population treated in our institution. Also, CHEK2 mutation was only identified in patients older than 60, which argues for more testing in patients in this age group. Approximately 9% of all IDC patients had a germline mutation compared to 4.2 % in patients with DCIS. Our review identifies that patients with BRCA1/2 mutations tend to undergo prophylactic mastectomy, and early testing likely impacted this decision. From our study, we believe that germline genetic testing should be offered to all breast cancer patients.
Associations between patient-reported nutritional status, survival, and toxicity among patients with limited stage small-cell lung cancer (LS SCLC) in a randomized trial of high-dose, twice-daily (BID) thoracic radiotherapy (TRT).
Authors: Evgenia Taranova, Bjorn H. Henning Gronberg, Tarje Onsøien Halvorsen, Kristin Toftaker Killingberg, Marit Slaaen, Marianne Aanerud
Journal: Journal of Clinical Oncology (2023)

8519 Background: Up to 1/3 of LS SCLC patients are cured by chemoradiotherapy (CRT), but severe toxicity is frequent and population-based studies show that many patients do not receive standard CRT. More knowledge on how to predict who experiences side-effects or achieves long term disease control is needed. Poor nutritional status is strongly associated with inferior survival in many types of cancer including non-small cell lung cancer, but little is known about whether this is the case in LS SCLC. We investigated whether nutritional status reported by patients on the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) was associated with toxicity and survival among participants in a trial comparing high dose with standard dose twice-daily TRT in LS-SCLC (NCT02041845, n=170). Methods: Patients received four courses of platinum/etoposide chemotherapy and were randomized to TRT of 60 Gy/40 fractions or 45 Gy/30 fractions. Patients completed PG-SGA SF before treatment commenced and were categorized as having low (PG-SGA SF score 0–3.9), intermediate (4.0–8.9) and high (≥9) risk of malnutrition. Toxicity was graded according to CTCAE 4.0. Median follow-up for survival was 49 months. Results: 113/170 (66.5%) patients completed PG-SGA SF at baseline. Median age was 65 years, 46.0% were men, 88.5% had PS 0-1, 87.6% stage III disease and 22.1% weight loss of &gt;5% the three months before inclusion. Median PG-SGA SF score was 3.0, 52.2% of patients had low, 29.2% intermediate, and 18.6% high risk of malnutrition. Numerically, there were more patients with stage III, PS 1-2 and pleural fluid among those at high risk. There was no difference in mean no. of chemotherapy courses (low: 3.85, intermediate: 3.88, high: 3.90, p=0.95) or TRT completion (low: 96.6%, intermediate: 97.0%, high: 95.2%, p=1.0). There were no statistically significant differences in proportions who experienced grade 3-4 toxicity (low: 88%, intermediate: 91%, high: 86%, p=0.86), median PFS (low: 15.1 months, intermediate: 11.8 months, high: NR, p=0.23), 2-year survival (low: 68%, intermediate: 52%, high: 67%, p=0.28) or median OS (low: 38.1 months, intermediate: 25.8 months, high: NR, p=0.15). Patients with weight loss &gt;5% did not experience more grade 3-4 toxicity (92% vs. 87%, p=0.73), had similar median PFS (24.0 vs. 15.9 months, p=0.69), 2-year survival (64.0% vs. 66.2%, p=0.84) and median OS (30.6 vs. 35.1 months, p=0.93) as those without. Conclusions: Our study suggest that LS SCLC patients tolerate and should receive concurrent chemotherapy and twice-daily TRT regardless of nutritional status and weight loss.
Examining ultrafine particle pollution and lung cancer risk in a large, diverse cohort.
Authors: Arthur Bookstein, Justine Po, Iona Cheng, Anna H. Wu, Timothy V. Larson, Lani Park, Jun Wu, Salma Shariff-Marco, Pushkar Inamdar, Veronica Wendy Setiawan, Mindy DeRouen, Scarlett L. Gomez, Loic Le Marchand, Daniel Stram, Jonathan Samet, Beate Ritz, Scott A. Fruin
Journal: Journal of Clinical Oncology (2023)

8532 Background: Health effects associated with particles less than 2.5 μm in diameter (PM 2.5 ) have been well studied, leading to the establishment of air quality standards and routine monitoring. Additionally, there is growing experimental evidence that ultrafine particles (UFPs), defined as particles less than 0.1µm in diameter, may adversely affect lung health, eliciting greater injury than larger particles due to deeper penetration into airways and longer retention in the lung parenchyma. Only two epidemiological studies have investigated this topic, finding no associations between ambient UFPs and respiratory mortality or overall lung cancer incidence respectively. Given the limited epidemiologic investigation of UFPs and lung cancer, we examined the association between airport-related UFPs and lung cancer incidence in a large, racially and ethnically diverse cohort. Methods: We estimated airport-related UFP exposure for 71,387 participants of the Multiethnic Cohort, who lived within a 53 km×43 km grid area around the Los Angeles International Airport (LAX) from date of cohort entry (1993-1996) through December 31, 2013. Cox proportional hazards regression was used, with calendar month/year as the time variable, to examine associations between UFP exposure and lung cancer risk adjusting for demographics, lifetime smoking, neighborhood socioeconomic status, occupation and lifestyle factors. Subgroup analyses were conducted by racial and ethnic groups, lung cancer histology, and smoking status. Co-pollutant models were run to mutually adjust for other traffic-related air pollutants. Results: A per unit increase in the interquartile range (IQR) of airport-related UFP exposure was not associated with lung cancer risk overall [HR = 1.01, 95% CI: 0.97-1.05] or by race and ethnicity. UFP exposure was suggestive of a positive association with risk of lung squamous cell carcinoma (SCC) [HR per IQR = 1.08, 95% CI: 1.00-1.17]. No associations were observed for other histologies [P het for histology = .05]. UFP exposure was associated with an increased SCC risk among current smokers [HR = 1.11, 95% CI: 1.01-1.22] but not among never or past smokers [P het for smoking = 0.51]. Conclusions: This study suggests a possible association between airport-related UFP exposure and risk of SCC. These results may be explained by previous studies finding that UFPs activate genes involved in oxidative damage, TNF-α signaling via NF-κB, and secretion of inflammatory and cardiopulmonary disease biomarkers. These findings warrant further investigation in large epidemiologic cohorts.
Identification of novel actionable SNVs using targeted comprehensive genome profiling in patients with sarcoma.
Authors: Mandar Bhonde, Chirantan Bose, Vineet Govinda Gupta, Priya Tiwari, Alain D'Souza, Trupti Kad, Sangeeta Prajapati, Bhagwat Jadhav, Kanchan Hariramani, Madhura Basavalingegowda, Fauzul Mobeen, Aditi Rani, Vatsal Mehra, Manoj Kumar Kumaran, Sumit Haldar, Rajat Saha, Prashant Mehta, Mohan Uttarwar, Jayant Khandare, Gowhar Shafi
Journal: Journal of Clinical Oncology (2023)

e23520 Background: The utility of comprehensive genome profiling is not well validated in early-stage sarcoma. The 5-year survival rate for metastatic sarcoma is less than 20%. The application of comprehensive Next Generation Sequencing (NGS) on tumor DNA has led to the identification of a multitude of actionable alterations in oncogenes &amp; tumor suppressor genes alongside the detection of immunotherapy markers like microsatellite instability, tumor mutational burden, and homologous recombinant deficiency. Methods: We retrospectively analyzed ccfDNA and gDNA in 13 sarcoma patients by targeted Next Generation Sequencing (NGS) using OncoIndx proprietary gene panel that targets exonic regions of 600 cancer-related genes. Illumina-compatible libraries were prepared by the target hybridization method and sequenced on Nextseq 2000 platform in a pair-end fashion. Variant calling was performed using an indigenously developed bioinformatics pipeline. Results: Here we report for the first time the identification of several, novel mutations in rare sarcomas such as IDH2R140W (in epithelioid hemangioendothelioma), CTNNB1D32V (in undifferentiated small round cell sarcoma) and DDR2M754I (in osteosarcoma). Furthermore, we observed, JAK1 amplification and BRAF-GUSBP1 fusion in osteosarcoma and a sarcomatoid carcinoma case, respectively. JAK1 amplification and DDR2M754I were found in the same patient. The IDH2 mutation and JAK1 amplification could find potential applications for JAK1 and IDH2 inhibitors respectively. Similarly, cancers having DDR2 mutations are known to respond to multikinase inhibitors such as Imatinib and Dasatinib, thus making a strong case for the potential repurposing of these drugs in sarcomas. ~93% of patients demonstrated genome-wide instabilities as evidenced by LOH, LST, TAI, and high TMB. Homologous Recombinant deficiency was found in 66.7% of patients. Although this is a small patient population, the high HRD+ percentages point to the underappreciated importance of HRD testing in sarcoma and herald the use of PARPi therapy for sarcoma. Conclusions: We identified several actionable mutations in rare sarcoma cases. These findings highlight the power of comprehensive genome profiling like the OncoIndx panel and warrant further studies on the role of IDH2, JAK1, and BRAF fusion in sarcomas. Moreover, they also present a strong potential case for repurposing of TKI such as Imatinib and Dasatinib in sarcomas.
Malnutrition risk at diagnosis and influence on survival in patients with solid tumors at a large academic cancer center.
Authors: Kunal C. Kadakia, James Thomas Symanowski, Aynur Aktas, Michele Szafranski, Jonathan C. Salo, Patrick L. Meadors, Ye Myint Aung, Declan Walsh
Journal: Journal of Clinical Oncology (2023)

6591 Background: Malnutrition is common in cancer patients and negatively impacts quality of life, tolerance to anti-cancer therapies and is associated with poor prognosis. It is, however, unclear if patient-reported malnutrition risk at initial diagnosis is related to overall survival (OS) in solid tumor oncology outpatients in the United States. Methods: A cohort of 3,562 patients who completed the malnutrition screening tool (MST), a validated assessment of malnutrition risk, at initial diagnosis of any stage solid tumor and had available survival data were analyzed. The primary objective was to evaluate the relationship of high malnutrition risk (≥2 of 5 = high risk for malnutrition, H-MST) to OS and was assessed using Kaplan Meier techniques and Cox proportional hazards models. Unadjusted analyses were performed, and adjusted multivariable analyses evaluated the impact of H-MST on OS controlling for key clinical baseline confounders. Results: The median age was 63 years (IQR: 54-71), with 62% females and 81% White. Most common cancer sites were breast (28%), gastrointestinal (GI, 21%), and thoracic (13%) and 80% were non-metastatic. Median follow up was 48.3 months. H-MST was associated with lower OS in the unadjusted model, median OS in months was 32.5 [H-MST] vs not reached in low MST [L-MST] (HR 3.3, 95% CI 2.9-3.7, p = &lt; 0.001). Multivariable analysis confirmed that H-MST remained independently associated with OS when controlling for age, sex, cancer site, stage, BMI, and symptom scores. Landmark OS rates at 50 months were 60% [H-MST] vs. 69% [L-MST] (HR 1.51 95% CI 1.3-1.7, p = &lt; 0.001). Adjusted subgroup analyses by cancer site showed the independent impact of H-MST was relatively similar across groups (Table). Conclusions: High malnutrition risk at initial diagnosis was independently associated with shorter survival across a large representative cohort of solid tumor oncology outpatients. The screening occurred before any anti-cancer therapy and it is noteworthy most had non-metastatic disease. These data highlight the need for systematic screening to identify patients at malnutrition risk who need additional assessment early during cancer. Further research on how to optimize allocation of limited nutrition resources for those with high malnutrition risk is needed. [Table: see text]
Integrating ayurveda rasayana therapy with standard of care therapies in patients with glioblastoma multiforme improves caregivers' quality of life: A prospective study.
Authors: Yogesh Narayan Bendale, Poonam Birari-Gawande, Anandrao Patil, Avinash Kadam, Yogesh Narayan Bendale
Journal: Journal of Clinical Oncology (2023)

e24001 Background: Caregivers of cancer patients frequently suffer from poor quality of life (QoL) due to stress related to caregiving. This stress is more severe in patients with very aggressive cancer which has the potential to negatively affect patients' functional independence. Glioblastoma multiforme (GBM) is an incurable disease with a poor prognosis. For caregivers of patients with glioblastoma, the burden of care can be high. Integration of conventional therapy with unconventional complimentary therapies which improves Patient reported outcome measures (PROM) can significantly improve caregivers' quality of life. Hence there is a great scope of integrative therapies while treating GBM patients. The present study was conducted with an aim of evaluating the impact of an Integrative cancer care program consisting of Ayurveda and Conventional standard of care in caregivers of patients with GBM. Methods: Caregivers of patients with high-grade GBM who opted for Ayurveda Rasayana therapy after a minimum of three months of starting conventional care for GBM were included in the study. Caregiver's Quality of life was evaluated using Caregiver’s QoL score (CarGOQoL) questionnaire at baseline and after 30, 60 and 90 days of initiating the Rasayana therapy. Results: The study included 21 male and 23 female caregivers with mean age 50.8 (±2.73) years. A total of 44 patients were included at baseline whereas at the sample size at day 30,60 and 90 were 40, 37, and 33 respectively. The CarGOQoL scores showed statistically significant improvement on day 30 ( P &lt; 0.05) which further improved on day 60 ( P&lt; 0.01) and then remained stable (Day 60 compared with day 90 P &gt; 0.05) on day 90. Conclusions: Caregivers of GBM showed improved QoL after integrating Ayurveda Rasayana therapy with conventional Standard of care therapies. Complimentary therapies that are known to improve PROMs in cancer patients can directly impact caregivers' QoL. Hence the possibility of an integrative approach should always be explored while treating GBM patients.
Return to work in breast cancer patients with and without pre-diagnosis psychological distress.
Authors: Tanmayi Pai, Christine Klassen, Sandhya Pruthi, Lauren Cornell
Journal: Journal of Clinical Oncology (2023)

e18883 Background: Women comprise more than 40% of the American workforce, with many women working at the time of a breast cancer diagnosis. Pre-diagnosis psychological distress is a rarely studied factor that may affect cancer survivors’ workforce participation and mental health status post treatment. In this 2-site prospective cohort study, we evaluated return to work (RTW) in breast cancer patients (pts) with and without reported pre-diagnosis stress. Methods: We enrolled 198 female pts at Mayo Clinic in Minnesota and Florida with newly diagnosed stage 0-III breast cancer who worked 35-plus hours/week at time of diagnosis. Pts were screened for eligibility at the intake visit. Eligible pts were emailed a baseline survey at the time of diagnosis, then a follow-up survey at 3 months. Surveys assessed demographics, work factors, treatment, and psychological distress per the validated Kessler Psychological Distress Scale (K6). Primary aims were to assess 1) the impact of pre-diagnosis psychological distress on RTW in pts with a breast cancer diagnosis and 2) the incidence of severe psychological distress (K6 ≥13) in those with and without delay in RTW. Wilcoxon rank sum tests were used to compare pts with and without pre-diagnosis stress at baseline and 3 months. Results: 189 and 142 pts took part in the baseline and 3-month surveys, respectively. Here, 40.7% of enrolled pts reported experiencing one or more major life stressors in the 18 months before diagnosis. At 3 months, 6 of the 75 pts who responded (8.0%) endorsed a delay in RTW after breast cancer diagnosis. Half of these pts (3/75) had reported a pre-diagnosis stressor, revealing no significant difference in time to RTW between the stressed and not-stressed groups. Median K6 at diagnosis in those with delay in RTW was 14 (range, 10-17), significantly higher than the median K6 of 9 in those without delay in RTW (range, 6-23; p = 0.026). 5/6 pts who reported delay in RTW had baseline or 3-month K6 ≥13. There was no significant difference in the number of pts with K6 ≥13 at baseline vs. 3 months (31.2% vs. 21.8%, p = 0.85). Overall, the pt population was well educated and well salaried. Conclusions: Pre-diagnosis psychological distress is prevalent, but it does not seem to be associated with delayed RTW in breast cancer pts; indeed, few pts reported a delay in RTW. Pts with delayed RTW after a breast cancer diagnosis had significantly higher median K6, generally ≥13. Thus, delay in RTW in breast cancer pts may be a surrogate marker of more serious psychological illness. Additional study in a socioeconomically diverse pt population is needed.
Immediate inpatient toxicities associated with CAR T-cell therapy: Real world data from a national inpatient sample.
Authors: Vinit Singh, Ahmad Al-alwan, vishakha sirpal, Farhan Khalid, Rajshree Gupta, Hussam Eltoukhy
Journal: Journal of Clinical Oncology (2023)

e18605 Background: Chimeric antigen receptor T-cell therapies (CAR-T) have shown overall survival benefits in multiple hematological malignancies. Since Tisageneleleucel's first approval in 2017 for ALL in pediatric and young adults, FDA has approved 5 CAR-T cell product for adult hematological malignancies all in refractory/relapsed setting. Cellular therapies are associated with severe immune related adverse events (IRAE) like Cytokine release syndrome (CRS), Immune effector-cell associated neurotoxicity (ICANS), and Hemophagocytic Lymphohistiocytosis (HLH). Limited real world data available for CAR T-cell associated immediate toxicity. CMS approved recent updates in ICD coding leading to better identification of IRAE in discharge data. We used NIS 2020 database with updated ICD codes to quantify immediate inpatient toxicity related to CAR T-Cell therapy. Methods: We identified patients with CAR T-cell from discharge data by utilizing ICD-10 procedure codes of CAR T-cell therapy for 5 approved products. Codes for acute lymphoblastic leukemia (ALL), DLBCL (diffuse large B-cell lymphoma), multiple myeloma (MM,) Follicular lymphoma (FH), Mantle Cell Lymphoma (MCL) were used to identify the indication. Patients without these indications were categorized as "Others". Appropriate weights were applied to the analyses to obtain national estimates. We analyzed in-hospital outcomes i.e Length of stay(days), and mortality. CAR T-cell related specific toxicity i.e CRS, ICANS, and HLH were identified and reported along with other complications. Cost to charge ratio adjusted hospitalization cost were estimated. Results: 2240 patients were identified on review of the NIS 2020 with 61.1% males, 74.11% NHW, mean age 57.54 years (95%CI 55.31-59.78), while 42.19% of the patients were age ≥65 years. 47.1% patients had private insurance while 39.06 % had Medicare. CAR-T cell was used for DLBCL in 60.94%, FH 2.23%, MCL 7.37%, MM 8.93% and ALL 9.38% patients respectively. The use of CAR-T was approximately equally distributed among four geographical regions of the United States. The mean length of stay was 19.4 days (17.05-21.75) and in patient mortality was observed in 3.79% of the patient population. The IRAE noted were CRS (17.19%), ICANS (12.5%) and HLH (2.46%). Other significant complications among patients were sepsis (9.15%), acute kidney injury (15.85%), Seizures (1.79%) and intubation (4.46%). Overall cost associated with the CAR-T therapy was found to be 270,446.9 (235670.5 - 305223.3). Conclusions: CAR-T therapy has appeared as a breakthrough in cancer management. Demographic variation is still an important issue and majority of the patients treated are white and have private insurance. DLBCL remains the most common target for CAR-T. Neurological syndromes remain significant adverse effects of the therapy and should be closely monitored.